Novartis's and Novo Nordisk's heart drugs lowered their targets in the blood but cut no heart attacks, full results show

The stories

11 on this beat today.

Every story told the same way: what happened, who is involved, why it matters, how it works, the truth and the good news.

1. 01

   Novartis's and Novo Nordisk's heart drugs lowered their targets in the blood but cut no heart attacks, full results show

   12.3% vs 12.1%

   of patients with a serious heart event, on pelacarsen and on a dummy

   over a typical 4.7 years of follow-up [1]

   236 to 64.4

   fall in Lp(a) after a year on pelacarsen

   on the dummy it stayed at 233.4 [1]

   1 in 5

   people who carry high Lp(a), mostly through their genes

   no approved drug lowers it much [4]

   What happened

   • Two big trials of new heart drugs failed to cut heart attacks, strokes or deaths, full results showed on Saturday. [2][3]
   • Both were shown at the American Heart Association's yearly meeting in Chicago. [2][3] A top medical journal printed them the same day. [2][3]
   • In Novartis's trial, 12.3% of patients on the drug had a heart attack, stroke or other serious heart event. [1] On a dummy drug, 12.1% did. [1]
   • Novartis's drug, pelacarsen, lowers Lp(a) in the blood. [1] Lp(a) is a particle that carries cholesterol, and high levels raise heart-attack risk. [4]
   • The drug did its job in the blood. [1] Lp(a) fell from 236 to 64.4 after 12 months, against 233.4 on the dummy. [1]
   • More than 8,300 adults in 42 countries took part, all with heart disease already. [15] The typical patient was followed for 4.7 years. [1]
   • Patients with higher Lp(a) at the start got no benefit either. [1] Among them, 12.3% had a heart event on the drug and on the dummy. [1]
   • Novo Nordisk's drug, ziltivekimab, is an antibody that lowers IL-6, a signal the body uses to cause inflammation. [3]
   • Inflammation can help build the plaques that clog arteries. [4]
   • The ZEUS trial cut IL-6 by 76%. [16] Yet 561 on the drug and 565 on the dummy had a heart attack, stroke or heart death. [16]
   • Novo stopped 2 other trials of the drug in September. [3] A trial monitoring committee had judged they were unlikely to succeed. [3]
   • Amgen and Eli Lilly, two US drug firms, are testing their own Lp(a) drugs in large trials. [4] Both lower Lp(a) further than pelacarsen did. [1]
   • Analysts at BMO Capital Markets had hoped for even a small edge for pelacarsen, as a good sign for rivals. [1] There was none. [1]
   • Amgen's trial takes only people with Lp(a) of 200 or more, and Lilly's 175 or more. [1] Novartis's took people from about 149. [1]

   Who is involved

   • Novartis a Swiss drugmaker; its Lp(a) drug pelacarsen, made with Ionis, cut no heart events
   • Novo Nordisk a Danish drugmaker; its anti-inflammation drug ziltivekimab cut no heart events
   • Amgen and Eli Lilly two US drugmakers; each is testing a drug that lowers Lp(a) further
   • Eli Lilly lepodisiran
   • The American Heart Association the heart group whose yearly meeting in Chicago showed the results

   How it unfolded

   1. Saturday Novartis and Novo full results
   2. Still to come Amgen and Lilly results
   3. July Novo's ZEUS trial misses, first told in brief [3]
   4. September Novartis says pelacarsen failed its big trial [4]
   5. September Novo stops 2 more ziltivekimab trials [3]
   6. Sat 7 Nov full results shown in Chicago and printed [2][3]

   Why it matters

   About 1 in 5 people carry high Lp(a), a risk passed down in families. [2] No approved drug lowers it much yet. [4]

   Heart doctors now wait for other Lp(a) trials to see whether the idea still has a future. [4]

   How it works

   Drug developers ask two questions: does a drug hit its target, and does that help patients? [1]

   Pelacarsen and ziltivekimab both passed the first test. [1][3] Neither passed the second, so heart events stayed the same. [1][3]

   Seen it before

   Fixing a dripping tap does not dry a damp wall if the water is coming through the roof.

   The truth

   • What is really going on Novartis and Novo Nordisk each lowered the thing their drug aimed at in the blood, Lp(a) and IL-6, and neither drug cut heart attacks, strokes or deaths. [1][3]
   • Why it works on people A blood number that plunges looks like a drug that works, because the number is the part anyone can see. [4]
   • Novartis paid for its trial. [2][15] Its patients already started at 236, above the cut-offs Amgen and Lilly use. [1]
   • About 21% on pelacarsen stopped it because of side effects, against just over 7% on the dummy. [15]
   • Who pays Amgen and Eli Lilly — Their own Lp(a) drugs now face harder questions before their big trials report. [1]
   • Who pays People with high Lp(a) — About 1 in 5 people carry it, and they still have no drug that lowers it. [2][4]
   • Nobody knows yet

     Why lowering Lp(a) did not help.

     NPR reports that Lp(a) may only be a sign of some other cause, and a Johns Hopkins cardiologist says treatment may need to start earlier. [14] A Copenhagen cardiologist thinks it harms through blood clotting. [4]

   • Nobody knows yet

     Whether Amgen's and Lilly's Lp(a) drugs will do better.

     Their trials have not reported; they take people with higher Lp(a), but Novartis's patients already started above those cut-offs. [1]

   • Nobody knows yet

     Whether blocking IL-6 helps people who are less sick.

     ZEUS patients also had serious kidney disease, and its lead researcher, Paul Ridker, says the drug may have come too late for them. [16] He says earlier trials of other anti-inflammation drugs did cut heart attacks. [16]

   What comes next

   Amgen's and Lilly's Lp(a) trials have not yet reported. [1] Their results are expected over the next few years. [14]

1. 02

   A lower blood pressure goal helps after a stroke

   What happened

   • A trial in Brazil tested a lower blood pressure goal for people who had had a stroke. [5]
   • Doctors usually aim for a top number under 140. [5] This trial aimed for 120 or lower. [5]
   • Over 4 years, 10.9% on the lower goal died or had a serious heart or stroke event, against 13.5%. [17]
   • A sister trial in people with type 2 diabetes found no benefit from the same lower goal. [5]
   • Both trials were printed in the New England Journal of Medicine. [5] They were shown at the heart meeting on Saturday. [5]

   Who is involved

   Gisele Sampaio of the Federal University of Sao Paulo led the trial, called OPTIMAL-STROKE. [5]

   • Gisele Sampaio led OPTIMAL-STROKE

   How it unfolded

   1. Saturday shown in Chicago
   2. Same day printed in a journal

   Why it matters

   About 1 in 3 stroke patients do not reach the blood pressure goals doctors already set. [5]

   How it works

   Doctors call the number they add pills to reach a treatment target.

   Aiming lower meant more medicine and lower pressure, and after a stroke, fewer deaths and heart events. [5]

   Seen it before

   Setting an alarm earlier gets you to school sooner only if the alarm was what made you late.

   Why a drug can only be judged against people who did not get it

   Clinical epidemiologists call it a control group: people given a dummy or the usual care, who show what would have happened without the drug.

   The twist

   A heart attack on a new drug proves nothing alone. Only the people on the dummy show how many heart attacks would have happened anyway.

   The picture

   On pelacarsen12.3%

   On a dummy12.1%

   Step by step

   1. 1 Give the drug to one group and a dummy to a similar group
   2. 2 Chance decides who gets which
   3. 3 Both groups face the same luck, care and season
   4. 4 Any gap between them is what the drug did
   5. 5 No gap means the drug did nothing, whatever the blood numbers say

   The same force, elsewhere today

   Where this chain is also running, in today's other stories.

   • One shot lowers two kinds of blood fat

     Arrowhead's falls of up to 65% are measured against each person's own start, not against the 10 people on the dummy, so nobody can yet say how much the drug did.

   • An old Ebola vaccine's cells spot the new strain

     Giving Ervebo to everyone would leave nobody unvaccinated to compare with, so a fall in cases could not be told apart from the outbreak passing its peak.

   • A heart drug helps teenagers in a trial

     Teenagers who started on the dummy were the comparison for the first 28 weeks, and their reading fell by a similar amount once they switched to Camzyos.

   • A lower blood pressure goal helps after a stroke

     Patients aimed at 120 were set against patients kept at 140, and only that comparison showed fewer deaths and heart events.

   Where you've seen this

   Schools

   a new reading scheme is judged fairly only against classes that kept the old one in the same year

   Farming

   a new fertiliser is tested on some plots while the plots beside them get none, under the same weather

   Online shops

   a shop shows a new advert to half its visitors to see whether they buy more than the other half

   The catch

   A control group only speaks for people like the ones in the trial. The same lower blood pressure goal helped stroke patients and did nothing for people with diabetes.

   And the whole of it

   Thousands of patients in these trials agreed to take what might be a dummy, for years. Every doctor who now decides about an Lp(a) or blood pressure pill is using an answer those patients gave, and none of them will ever know which pill they had.

   The truth

   • What is really going on On the same day, at the same meeting, an old approach did help: aiming for a lower blood pressure after a stroke meant fewer deaths and heart events. [5]
   • Kidney problems rose on the lower goal. [17] In the diabetes trial they reached 5.7% of patients, against 3.7% on the usual goal. [18]
   • Shawna Nesbitt of UT Southwestern said doctors may have been "lumping patients together" in ways that do not always help. [5]
   • Who gains Stroke patients treated to a lower goal — In the Brazilian trial, aiming for 120 instead of 140 meant fewer deaths and heart events over 4 years. [5]
   • Nobody knows yet

     Whether the lower blood pressure goal really fails in diabetes.

     The lower goal cut serious events by about 10%, 286 people against 315, a gap too small to be sure of. [18] The trial's steering committee chair says even 9,476 patients may be too few to show a modest benefit. [18]

   Good news

   • Second strokes fell to 4.7% of people on the lower goal, from 6.4% on the usual one. [17]
   • After a stroke, aiming for a top blood pressure number of 120 instead of 140 meant fewer deaths and heart events over 4 years, in a trial in Brazil.

1. 03

   A cheap water pill given early after a stroke

   What happened

   • A trial called REDUCE gave spironolactone, a cheap water pill, to people right after a stroke. [5]
   • Doctors usually give it late, after 3 other blood pressure drugs have failed. [5]
   • After 3 months, 52% on it had blood pressure under 130 over 80, against 30% on usual care. [19]

   Who is involved

   Jordana Cohen of the University of Pennsylvania led the trial. [5]

   • Jordana Cohen led REDUCE

   Why it matters

   A year after a stroke, about 1 in 5 survivors have stopped their blood pressure pills, a stroke expert said. [5]

   How it works

   REDUCE measured blood pressure as its main result, not strokes or deaths. [5]

   It leans on an older finding: a fall of just 7 points has been linked to 38% fewer second strokes. [5]

   Seen it before

   A coach times your runs instead of waiting for race day, because faster times usually mean better races.

   The truth

   • The trial has only been shown as a short summary and is not yet printed in a journal. [5]
   • Nobody knows yet

     Whether spironolactone after a stroke prevents second strokes.

     REDUCE measured only blood pressure, and it is not yet printed in a journal. [5]

   Good news

   • Spironolactone is cheap and already known to many doctors, Bruce Ovbiagele of the University of California, San Francisco, said. [5]
2. 04

   A Welsh family faces a 2.95 million pound bill

   What happened

   • A family in Swansea, Wales, has found a gene therapy for their son costs about 2.95 million pounds. [7]
   • Tate McDaid, 5, has Sanfilippo syndrome, a rare illness often called childhood dementia. [7]
   • It slowly takes away abilities such as walking and eating. [7] It can move faster after age 5. [7]
   • Just over 100 UK children have it, one count says. [7] A charity for the illness puts it at about 140. [7]
   • His mother Tammy has raised more than 160,000 pounds, about 5% of the 2.95 million pounds. [7]

   How it unfolded

   The US approved the treatment, Ultragenyx's Fayuvi, in September. [7] Its US price is 3.95 million dollars. [7]

   1. September US approves Fayuvi
   2. Now a family abroad seeks the money
   3. Now Cardiff doctors talk to the US
   4. This month Tate turns 6

   Why it matters

   The treatment is not yet available in the UK. [7] His mother says it works less well as he gets older. [7]

   The truth

   • Ultragenyx said there is "not a single estimate" it can give for a patient from abroad. [7]
   • Who gains Ultragenyx — It sets Fayuvi's US price at 3.95 million dollars, and families abroad must find a similar sum to reach it. [7]
   • Who pays Tate McDaid's family — They have raised about 5% of the 2.95 million pounds needed for the gene therapy. [7]
   • Nobody knows yet

     What Fayuvi would cost a family outside the US.

     Ultragenyx says its costs depend on each child's needs and the hospital, and gives no single figure. [7]

   What comes next

   Doctors at Noah's Ark Children's Hospital in Cardiff are talking to US officials for the family. [7] Tate turns 6 this month. [7]

3. 05

   WHO counts 10,668 Ebola cases in Congo

   What happened

   • By 3 November, Congo had confirmed 10,668 Ebola cases, including 5,198 deaths, the World Health Organization said. [8]
   • This outbreak is of Bundibugyo virus, a less common kind of Ebola. [9]
   • In the 21 days to 3 November, 1,463 new cases were confirmed. [8] Ituri province had 710 of them and Nord Kivu 640. [8]
   • Of 512 deaths since 21 October, 335 were in communities and 177 in treatment centres. [8]

   Why it matters

   Kenya and Nigeria reported no new cases, but WHO says the region must stay ready. [8]

   How it works

   Outbreak experts call the job case detection: finding each sick person early enough to treat them.

   WHO says the many deaths outside clinics, often of young children, show cases are found too late. [8]

   Seen it before

   A smoke alarm only helps if it goes off while there is still time to get out.

   The truth

   • Who pays Families in Congo's outbreak zones — Many deaths, often of young children, happen in communities before the sick reach care. [8]
   • Nobody knows yet

     How many Ebola cases are being missed in Congo.

     The count is of confirmed cases, and 335 of 512 recent deaths happened in communities, outside treatment centres. [8]

   Good news

   • WHO counts 2,881 people who have recovered in this outbreak. [8]
4. 06

   An old Ebola vaccine's cells spot the new strain

   What happened

   • German researchers found that Ervebo, an approved Ebola vaccine, trains immune cells that also recognise Bundibugyo virus. [9]
   • Ervebo was made for a different kind, Zaire Ebola, not the one spreading in Congo now. [9]
   • "We now know that the immune cells can most likely also recognize the Bundibugyo virus," Mayer said. [9]
   • But her data cannot show whether that response protects people from illness. [9]

   Who is involved

   Leonie Mayer of the German Center for Infection Research led the study. [9]

   • Leonie Mayer German Center for Infection Research

   How it unfolded

   1. Now Tumaini trial in Congo
   2. Mid-2027 wide use, perhaps

   Why it matters

   So doctors cannot simply give Ervebo to everyone in Congo, Mayer explains. [9]

   How it works

   If everyone got Ervebo and cases fell, nobody could tell whether the vaccine did it. [9]

   Cases can also fall because of other measures, or because the outbreak has passed its peak. [9]

   Seen it before

   If a whole class gets a new tutor the week before an easy test, nobody knows if the tutor helped.

   Giving Ervebo to everyone would leave nobody unvaccinated to compare with, so a fall in cases could not be told apart from the outbreak passing its peak.

   The idea, in story 02: Why a drug can only be judged against people who did not get it →

   The truth

   • Jurgen May of the Bernhard Nocht Institute warned that mass use could "forfeit trust". [9]
   • Nobody knows yet

     Whether Ervebo protects anyone against Bundibugyo Ebola.

     The lab study saw immune cells recognise the virus, and its own lead author says it cannot show protection. [9]

   What comes next

   The Tumaini trial in Congo is testing Ervebo and a Moderna vaccine against this strain. [9] Wide use may not come before mid-2027. [9]

5. 07

   The Netherlands gives WHO 17 million euros

   What happened

   • The Netherlands is giving the World Health Organization 7 million euros for its Ebola response in Congo. [10]
   • It is also giving a new 10 million euros that WHO can spend on any future emergency. [10]
   • That comes on top of the 9.6 million euros a year it already gives WHO. [10]

   Who is involved

   WHO's head, Tedros Adhanom Ghebreyesus, and Dutch minister Sjoerd Sjoerdsma announced it in a joint article. [10]

   • Tedros Adhanom Ghebreyesus head of WHO
   • Sjoerd Sjoerdsma Dutch development minister

   How it unfolded

   Funding for global health, including for WHO, is falling, the two write. [10]

   Why it matters

   Money WHO can move fast lets it respond before an outbreak grows, they argue. [10]

   How it works

   Aid givers call money not tied to one use unearmarked, so WHO can send it where it is needed most. [10]

   The 7 million euros is tied to Ebola. [10] The 10 million can go to whatever threat comes next. [10]

   Seen it before

   Pocket money saved for one school trip pays only for that trip, while savings pay for whatever comes up.

   The truth

   • Who gains The World Health Organization — The Dutch 10 million euros is not tied to one use, so WHO can send it to the next emergency. [10]

   Good news

   • The Netherlands is giving the World Health Organization 7 million euros for the Ebola response in Congo, and 10 million more for whatever emergency comes next.
6. 08

   A heart drug helps teenagers in a trial

   What happened

   • The drugmaker Bristol Myers Squibb says its drug Camzyos helped teenagers with a disease that blocks blood leaving the heart. [11]
   • Of 43 teenagers who finished the first 28 weeks, 23 had the drug and 20 a dummy. [11]
   • After 28 weeks, everyone took the drug until week 56. [11]
   • After 56 weeks on the drug, a pressure reading of how blocked the heart's exit is fell by 48.1 points. [11]
   • Teenagers first given the dummy saw a similar fall once they switched to the drug. [11]

   How it unfolded

   1. First 28 weeks drug or dummy
   2. Weeks 28 to 56 everyone on the drug

   Why it matters

   The company says it is the first long, double-blind trial of this kind of drug in teenagers. [11]

   How it works

   Camzyos blocks cardiac myosin, calming a heart that squeezes too hard, which is the source of the illness. [11]

   A gentler squeeze leaves the heart's exit less blocked, the company says. [11]

   Seen it before

   Pressing a garden hose less hard lets more water through the nozzle.

   Teenagers who started on the dummy were the comparison for the first 28 weeks, and their reading fell by a similar amount once they switched to Camzyos.

   The idea, in story 02: Why a drug can only be judged against people who did not get it →

   The truth

   • These results come from the company's own announcement at a doctors' meeting, not a journal. [11]
   • Who gains Bristol Myers Squibb — A placebo-controlled trial in teenagers gives doctors evidence to use Camzyos in younger patients. [11]

   Good news

   • Teenagers with a disease that blocks blood leaving the heart saw the blockage fall on Camzyos over 56 weeks, with few serious side effects.
7. 09

   One shot lowers two kinds of blood fat

   What happened

   • Arrowhead Pharmaceuticals gave single doses of a new drug, ARO-DIMER-PA, to 21 people, and a dummy to 10. [13]
   • It aims at 2 proteins that handle fat in the blood, PCSK9 and APOC3, with one drug. [13]
   • LDL cholesterol fell by 26% to 65%, depending on the dose. [13] Triglycerides, another blood fat, fell by 56% to 78%. [13]
   • The results were shown at the American Heart Association's meeting. [13]

   How it unfolded

   1. Now single doses tested
   2. Later longer studies

   Why it matters

   Arrowhead calls it proof that one RNA drug can hit both targets at once. [13]

   Amgen's and Lilly's Lp(a) drugs are also RNA drugs of this kind, called siRNA. [1]

   How it works

   Arrowhead's falls of up to 65% are measured against each person's own start, not against the 10 people on the dummy, so nobody can yet say how much the drug did.

   The idea, in story 02: Why a drug can only be judged against people who did not get it →

   The truth

   • The falls are against each person's starting level and are not compared with the dummy group, the company notes. [13]
   • Nobody knows yet

     How much of ARO-DIMER-PA's effect is the drug.

     Arrowhead's falls are against each person's start and are not yet set against the 10 people given a dummy. [13]

   What comes next

   Longer studies are needed to show any heart benefit, the company says. [13]

8. 10

   Biotech groups sue to stop a Medicare price plan

   What happened

   • BIO, a biotech industry group, and 2 California biotech groups sued on Friday to stop a US drug-price plan. [6]
   • The plan, called GLOBE, would tie what the US Medicare programme pays for drugs to prices in similar countries. [6]
   • The groups say GLOBE goes beyond what the law lets Medicare do. [6] They asked a federal court in northern California to halt it. [6]

   Why it matters

   BIO is joining a legal fight against GLOBE that others had already started. [6]

   How it works

   Lawyers call this a question of statutory authority: whether a law gave an agency the power it uses. [6]

   Seen it before

   A school prefect can hand out detentions only if the head teacher gave them that power.

   The truth

   • The Centers for Medicare and Medicaid Services did not answer at first. [6]
   • Who gains Biotech companies in BIO — If the court halts GLOBE, Medicare would not tie what it pays them to prices in other countries. [6]
   • Nobody knows yet

     Whether a court will stop GLOBE.

     The case was filed only on Friday, and the agency that runs Medicare had not answered. [6]

9. 11

   A heart valve trial waits longer for its answer

   What happened

   • Kardigan, a drug company, will measure its trial's main result at week 48, to allow more time. [12] It will take an inside look at week 24. [12]
   • Its drug, ataciguat, is being tested in aortic stenosis, where calcium builds up on a heart valve. [12]
   • The trial has enrolled 156 people. [12]
   • In records of about 45,000 patients, 27% got worse quickly. [12]

   How it unfolded

   1. Week 24 an inside look only
   2. Week 48 the main result

   Why it matters

   In those records, fast worsening went with more valve replacements, hospital stays and heart failure. [12]

   How it works

   Calcium builds up at each patient's own rate, the company found. [12] So one calcium scan shows a patient's risk, but not how fast the valve is worsening. [12]

   Seen it before

   One photo shows how tall a child is, but only two photos a year apart show how fast they grow.

   The truth

   • These findings come from the company's own announcement. [12]